metallothionein and Bone-Diseases

Cadmium has been shown to manifest its toxicity in human and animals by mainly accumulating in almost all of the organs and kidney is the main target organ where it is concentrated mainly in cortex. Environmental exposure of cadmium occurs via food, occupational industries, terrestrial and aquatic ecosystem. At molecular level, cadmium interferes with the utilization of essential metals e.g. Ca, Zn, Se, Cr and Fe and deficiencies of these essential metals including protein and vitamins, exaggerate cadmium toxicity, due to its increased absorption through the gut and greater retention in different organs as metallothionein (Cd-Mt). Cadmium transport, across the intestinal and renal brush border membrane vesicles, is carrier mediated and it competes with zinc and calcium. It has been postulated that cadmium shares the same transport system. Cadmium inhibits protein synthesis, carbohydrate metabolism and drug metabolizing enzymes in liver of animals. Chronic environmental exposure of cadmium produces hypertension in experimental animals. Functional changes accompanying cadmium nephropathy include low molecular weight proteinuria which is of tubular origin associated with excess excretion of proteins such as beta 2 microglobulin, metallothionein and high molecular weight proteinuria of glomerular origin (excretion of proteins such as albumin IgG, transferrin etc.). Recent data has shown that metallothionein is more nephrotoxic to animals. Cadmium is also toxic to central nervous system. It causes an alterations of cellular functions in lungs. Cadmium affects both humoral and cell mediated immune response in animals. Cadmium induces metallothionein in liver and kidney but under certain nutritional deficiencies like protein-calorie malnutrition and calcium deficiency, enhanced induction and greater accumulation of cadmium metallothionein has been observed.

Topics: Aging; Animals; Bone Diseases; Cadmium; Calcium; Central Nervous System Diseases; Chromium; Copper; Dietary Proteins; Drug Interactions; Environmental Exposure; Female; Half-Life; Humans; Hypertension; Immunity; Intestinal Absorption; Intestinal Diseases; Iron; Kidney Diseases; Liver; Lung; Male; Metallothionein; Ovary; Selenium; Sex Factors; Testis; Tissue Distribution; Vitamins; Zinc

To observe the relationship between urinary metallothionein excretion and osteal damage induced by cadmium in a general population.. The inhabitants living in both cadmium polluted and non-polluted areas were asked to participate in this study. Urinary cadmium (UCd) and blood cadmium (BCd) were measured by GF-AAS. Total cadmium(TCd)was evaluated with environmental cadmium exposure. URBP, UB2M, UALB and UMT were measured by ELISA method. UNAG, UNAGB were measured by fluorescence analysis method. Forearm bone mineral density in human were mensurated by SPA.. UMT can reflect the change of cadmium body burden. Renal dysfunction and osteoporosis would appear successively after high level of cadmium exposure. UMT had a complex relationship with bone mineral density which related to the amount of UMT excretion. The BMDLs of UCd were calculated using software of BMDS Versionl. 3.2 for these biomarkers. The values of BMDL of these biomarkers were arranged: UNAGB < UNAG < UB2M < UMT < URBP < Tscore < UALB.. Cadmium exposure could induce bone damage which occurred later than renal dysfunction related to cadmium exposure. UMT could be not only a specific and sensitive biological indicator of cadmium-induced renal dysfunction but also could reflect the damage on bone induced by cadmium.

Topics: Adult; Aged; Biomarkers; Bone Density; Bone Diseases; Cadmium; Environmental Exposure; Female; Humans; Kidney Diseases; Male; Metallothionein; Middle Aged

Exposure to cadmium (Cd) can result in nephrotoxicity and osteotoxicity. Because Cd-induced nephrotoxicity involves oxidative stress and caloric restriction decreases oxidative stress, we examined whether reduced caloric intake will protect against Cd-induced nephrotoxicity. In addition, the protection against the osteotoxicity was also examined. Male and female Sprague-Dawley rats were provided drinking water containing 100 mg Cd/l. Since fluid intake relative to the body weight was higher in females as compared to the males, the Cd concentration in their water was reduced to 80 mg/l after 3 months and 65 mg/l after 6.5 months. During the 27 month exposure period the males and females consumed a total of about 5 g Cd/kg body weight. Food was restricted to 20 g/day after the first 3 months. During the unrestricted food intake period Cd exposure reduced the bone density in females by 23%, with a partial recovery and stabilization during the caloric restriction phase. Hepatic and renal Cd accumulation and corresponding metallothionein (MT) levels were very similar in both sexes. The reported critical Cd concentration for nephrotoxicity was reached by 9 months. Renal MT levels were maximum at this time. Despite a 1.5-fold increase in renal Cd concentration over the next 18 months, there was no significant increase in renal MT levels. In spite of high renal Cd levels and lack of availability of sufficient MT, there was no sign of nephrotoxicity, as measured by urinary protein and glucose excretion. It is concluded that caloric restriction prevents Cd-induced nephrotoxicity and also appears to control the osteotoxicity of Cd.

Topics: Animals; Body Weight; Bone Density; Bone Diseases; Cadmium; Drinking; Energy Intake; Female; Kidney; Kidney Diseases; Liver; Male; Metallothionein; Rats; Rats, Sprague-Dawley; Sex Factors